Medication effects on pulmonary thromboembolism in mice intravenously transplanted with canine adipose tissue-derived mesenchymal stem cells

Importance: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is a promising regenerative therapy, but it can lead to severe complications, including pulmonary thromboembolism (PTE).

Objective: As part of an ongoing study, this study examined the impact of medications, such as heparin, aspirin, and sodium nitroprusside (SNP), on the factors linked to PTE after an intravenous injection of canine mesenchymal stem cell into experimental animals.

Methods: Fluorescently labeled canine AdMSCs were administered intravenously into the tail veins of five-week-old male BALB/c hairless mice. This study compared the survival rates, biodistribution, platelet counts, D-dimer levels, and histological examination results among the drug treatment experimental and the control groups.

Results: The final survival rates in the SNP, control aspirin, and heparin groups were 25%, 33%, 50%, and 100%, respectively. Ex vivo imaging confirmed fluorescence exclusively in the lungs of all subjects who died during the injection, with no fluorescence detected in the other organs. On the other hand, in the heparin experimental group, the surviving individuals exhibited fluorescence in the lungs and the liver on day one. Histological biopsies revealed PTE in all deceased individuals within the medication experimental groups (p = 0.029).

Conclusions and relevance: Heparin was highly effective, with no PTE-related deaths observed when used alongside cell injections. Aspirin revealed moderate effectiveness, surpassing the control group. On the other hand, the efficacy of SNP was inferior to that of the other two drugs.